Sudden Death in a Traveler Following Halofantrine Administration
---Togo, 2000

On July 17, 2000, a previously healthy 22-year-old U.S. student collapsed and
died suddenly while leading a teenage exchange group in West Africa. This
report summarizes the results of the investigations of this incident, which implicate use
of halofantrine for treatment of malaria as the cause of death. Travelers should
be warned that halofantrine treatment may be dangerous in persons with
cardiac abnormalities or in those taking mefloquine for malaria prophylaxis.

The student began taking mefloquine for malaria prophylaxis approximately
1 week before departure on July 5. On July 12, he developed fever of 102 F (39 C),
chills, headache, and cough, and was seen at a clinic in Togo 2 days later. He was
diagnosed with malaria and bronchopneumonia and treated orally with
halofantrine, dirithromycin, and acetylcysteine. The patient defervesced over the following 24
hours and resumed normal activities on July 13.

On July 14, following a 2-hour car ride, he stepped from the car, complained of
a "head rush," and collapsed. Cardiopulmonary resuscitation was unsuccessful, and
he was later pronounced dead at a local medical center. On July 24, an autopsy
was performed at Yale-New Haven Medical Center, which revealed a
previously undiagnosed atypical asymmetric hypertrophic cardiomyopathy.

Editorial Note:

This report underscores precautions about halofantrine use
for treating malaria, especially among travelers who are taking mefloquine
prophylaxis. In the case of this traveler, who had been taking mefloquine for prophylaxis and
had been in a malarious area for only 1 week, the diagnosis of malaria probably
was erroneous. The patient in this report also received dirithromycin, a
macrolide antibiotic that may have exacerbated the cardiac effects of mefloquine
and halofantrine (1).

Halofantrine is a synthetic phenanthrene-methanol antimalarial and is
chemically related to quinine and mefloquine. The drug has been approved for use in the
United States and is marketed internationally but not in the United States.
Although halofantrine is an efficacious treatment for
Plasmodium falciparum malaria (2),
the drug can cause rare but serious cardiac complications
(3). The drug has been associated with lengthening of the QT interval in patients without known
cardiac abnormalities (4--6) and with fatal or near-fatal arrhythmias in some persons
(6,7). Although this patient had no family history of heart disease,
hypertrophic cardiomyopathy, which has been associated with QT
prolongation and an increased risk for sudden cardiac death
(8), was discovered at autopsy.

QT prolongation may occur more frequently when halofantrine is
administered following mefloquine (6), and prescribing information for halofantrine warns against
its use in those taking mefloquine (9). The manufacturer and others also recommend
that halofantrine be used for treatment only in persons who have a
normal
electrocardiogram, which makes its use in many less-developed settings
impractical (4,9).

Travelers to remote areas should consider carrying antimalarials for
presumptive self-treatment should they become ill with symptoms of malaria and are unable
to obtain prompt medical care. Both sulfadoxine-pyrimethamine (Fansidar*,
Roche Laboratories, Nutley, New Jersey), and atovaquone-proguanil (Malarone,
Glaxo Wellcome, Research Triangle Park, North Carolina) are acceptable options
for presumptive self-treatment, depending on local drug resistance patterns
(10). However, all travelers should be cautioned that
presumptive self-treatment for malaria is not a substitute for a prompt medical evaluation.

Halofantrine treatment may be dangerous in those with cardiac abnormalities or
in those taking mefloquine for malaria prophylaxis. However, because
P. falciparum malaria is a potentially life-threatening illness, the benefit of halofantrine
treatment may outweigh the risks in the case of laboratory-confirmed
P. falciparum infection if no other effective therapies are available. Additional information about
malaria prophylaxis and treatment is available from CDC by telephone, (888) 232-3228,
fax, (888) 232-3299, or on the World-Wide Web, http://www.cdc.gov/travel.

* Use of trade names is for identification only and does not imply endorsement by CDC or
the U.S. Department of Health and Human Services.

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